The overall objective of this Program Project Grant is to study the regulation of circulation in pathological states. The Program represents the coordinated effort of clinical and basic investigators to study the cellular and cardiovascular control mechanisms underlying abnormalities of circulatory regulation in pathologic states such as hypertension, cardiac hypertrophy and failure, myocardial ischemia and various abnormal circulatory states. The research on cellular mechanisms includes studies on the electro-physiologic properties and reactivity of arterial muscle in hypertension, the biochemical determinants of contraction in vascular and cardiac muscle, and the regulation of chloride transport. The research into cardiovascular control mechanisms emphasizes neurohumoral and renal factors in pathologic states and the regulation of myocardial performance during ischemia and mechanical stresses. The goals of the supplement are 1) to provide additional core resources and facilities and tighten the cohesion of this interdisciplinary program; 2) to reinforce the recent basic direction of the program into cellular mechanisms; and 3) to develop and study new animal models of hypertension and heart failure; and 3) to develop and study new animal models of hypertension and heart failure. The proposals, which involve mostly current participants, complement the ongoing research in three areas: I. Autonomic control in hypertension, II. Autonomic and cellular mechanisms in myocardial hypertrophy and failure, and III. Humoral and renal control mechanisms.